This research grant proposal is developed as a joint effort of the Division of Urology (Department of Surgery) and the Human Immunobiology Group in the Department of Microbiology and Immunology to 1) obtain comprehensive knowledge about the effect of bladder cancer on important host defense mechanisms (the immune system and inflammatory processes) and on the specific immune response to this cancer; 2) explore new therapeutic approaches to bladder cancer by direct immune manipulations (immunotherapy); and 3) search for viral agents that may contribute to the etiology of this tumor. Specific cellular immunity will be quantified by in vitro assays using tissue culture lines of bladder cancer (T-24 and others). The type cell(s) responsible for CMI will be identified. Specific antibody to tumor will be sought by LDA(ADCC) and C dependent cytotoxicity tests. The effect of tumor stage on specific B and T lymphoid cell and macrophage functions will be evaluated with special reference to prognostic significance. The effects of conventional therapy (surgery, radiation and chemotherapy) as well as new approaches to immunotherapy on the immune system and on specific response to tumor antigens will be studied. The clinical value of Adjuvant and specific immunotherapy will be determined. Bladder cancer in animals will be used to explore new immunotherapeutic maneuvers prior to clinical trial. Preliminary work performed in the past year or more has laid the necessary groundwork for the extensive and integrated work proposed here.